Browsing by Subject "CARRIERS"

Sort by: Order: Results:

Now showing items 1-13 of 13
  • Wannasarit, Saowanee; Wang, Shiqi; Figueiredo, Patricia; Trujillo Olvera, Claudia Ximenia; Eburnea, Francesca; Simón-Gracia, Lorena; Correia, Alexandra; Ding, Yaping; Teesalu, Tambet; Liu, Dongfei; Wiwattanapatapee, Ruedeekorn; Santos, Hélder A.; Li, Wei (2019)
    Achieving cellular internalization and endosomal escape remains a major challenge for many antitumor therapeutics, especially macromolecular drugs. Viral drug carriers are reported for efficient intracellular delivery, but with limited choices of payloads. In this study, a novel polymeric nanoparticle (ADMAP) is developed, resembling the structure and functional features of a virus. ADMAP is synthesized by grafting endosomolytic poly(lauryl methacrylate‐co‐methacrylic acid) on acetalated dextran. The endosomolytic polymer mimics the capsid protein for endosomal escape, and acetalated dextran resembles the viral core for accommodating payloads. After polymer synthesis, the subsequent controlled nanoprecipitation on a microfluidic device yields uniform nanoparticles with high encapsulation efficiency. At late endosomal pH (5.0), the ADMAP particles successfully destabilize endosomal membranes and release the drug payloads synergistically, resulting in a greater therapeutic efficacy compared with that of free anticancer drugs. Further conjugation of a tumor‐penetrating peptide enhances the antitumor efficacy toward 3D spheroids and finally leads to spheroid disintegration. The unique structure along with the synergistic endosomal escape and drug release make ADMAP nanoparticles favorable for intracellular delivery of antitumor therapeutics.
  • Bogacheva, Mariia; Egorova, Anna; Slita, Anna; Maretina, Marianna; Baranov, Vladislav; Kiselev, Anton (2017)
    The major barriers for intracellular DNA transportation by cationic polymers are their toxicity, poor endosomal escape and inefficient nuclear uptake. Therefore, we designed novel modular peptide-based carriers modified with SV40 nuclear localization signal (NLS). Core peptide consists of arginine, histidine and cysteine residues for DNA condensation, endosomal escape promotion and interpeptide cross-linking, respectively. We investigated three polyplexes with different NLS content (10 mol%, 50 mol% and 90 mol% of SV40 NLS) as vectors for intranuclear DNA delivery. All carriers tested were able to condense DNA, to protect it from DNAase I and were not toxic to the cells. We observed that cell cycle arrest by hydroxyurea did not affect transfection efficacy of NLS-modified carriers which we confirmed using quantitative confocal microscopy analysis. Overall, peptide carrier modified with 90 mol% of SV40 NLS provided efficient transfection and nuclear uptake in non-dividing cells. Thus, incorporation of NLS into arginine-rich cross-linking peptides is an adequate approach to the development of efficient intranuclear gene delivery vehicles. (C) 2017 Elsevier Ltd. All rights reserved.
  • Patel, V.L.; Busch, E.L.; Friebel, T.M.; Cronin, A.; Leslie, G.; McGuffog, L.; Adlard, J.; Agata, S.; Agnarsson, B.A.; Ahmed, M.; Aittomäki, K.; Alducci, E.; Andrulis, I.L.; Arason, A.; Arnold, N.; Artioli, G.; Arver, B.; Auber, B.; Azzollini, J.; Balmaña, J.; Barkardottir, R.B.; Barnes, D.R.; Barroso, A.; Barrowdale, D.; Belotti, M.; Benitez, J.; Bertelsen, B.; Blok, M.J.; Bodrogi, I.; Bonadona, V.; Bonanni, B.; Bondavalli, D.; Boonen, S.E.; Borde, J.; Borg, A.; Bradbury, A.R.; Brady, A.; Brewer, C.; Brunet, J.; Buecher, B.; Buys, S.S.; Cabezas-Camarero, S.; Caldes, T.; Caliebe, A.; Caligo, M.A.; Calvello, M.; Campbell, I.G.; Carnevali, I.; Carrasco, E.; Chan, T.L.; Chu, A.T.W.; Chung, W.K.; Claes, K.B.M.; Cook, J.; Cortesi, L.; Couch, F.J.; Daly, M.B.; Damante, G.; Darder, E.; Davidson, R.; De La Hoya, M.; Della Puppa, L.; Dennis, J.; Díez, O.; Ding, Y.C.; Ditsch, N.; Domchek, S.M.; Donaldson, A.; Dworniczak, B.; Easton, D.F.; Eccles, D.M.; Eeles, R.A.; Ehrencrona, H.; Ejlertsen, B.; Engel, C.; Evans, D.G.; Faivre, L.; Faust, U.; Feliubadalo, L.; Foretova, L.; Fostira, F.; Fountzilas, G.; Frost, D.; García-Barberan, V.; Garre, P.; Gauthier-Villars, M.; Geczi, L.; Gehrig, A.; Gerdes, A.-M.; Gesta, P.; Giannini, G.; Glendon, G.; Godwin, A.K.; Goldgar, D.E.; Greene, M.H.; Gutierrez-Barrera, A.M.; Hahnen, E.; Hamann, U.; Hauke, J.; Herold, N.; Hogervorst, F.B.L.; Honisch, E.; Hopper, J.L.; Hulick, P.J.; Izatt, L.; Jager, A.; James, P.; Janavicius, R.; Jensen, U.B.; Jensen, T.D.; Johannsson, O.Th.; John, E.M.; Joseph, V.; Kang, E.; Kast, K.; Kiiski, J.I.; Kim, S.-W.; Kim, Z.; Ko, K.-P.; Konstantopoulou, I.; Kramer, G.; Krogh, L.; Kruse, T.A.; Kwong, A.; Larsen, M.; Lasset, C.; Lautrup, C.; Lazaro, C.; Lee, J.; Lee, J.W.; Lee, M.H.; Lemke, J.; Lesueur, F.; Liljegren, A.; Lindblom, A.; Llovet, P.; Lopez-Fernandez, A.; Lopez-Perolio, I.; Lorca, V.; Loud, J.T.; Ma, E.S.K.; Mai, P.L.; Manoukian, S.; Mari, V.; Martin, L.; Matricardi, L.; Mebirouk, N.; Medici, V.; Meijers-Heijboer, H.E.J.; Meindl, A.; Mensenkamp, A.R.; Miller, C.; Gomes, D.M.; Montagna, M.; Mooij, T.M.; Moserle, L.; Mouret-Fourme, E.; Mulligan, A.M.; Nathanson, K.L.; Navratilova, M.; Nevanlinna, H.; Niederacher, D.; Cilius Nielsen, F.C.; Nikitina-Zake, L.; Offit, K.; Olah, E.; Olopade, O.I.; Ong, K.-R.; Osorio, A.; Ott, C.-E.; Palli, D.; Park, S.K.; Parsons, M.T.; Pedersen, I.S.; Peissel, B.; Peixoto, A.; Perez-Segura, P.; Peterlongo, P.; Petersen, A.H.; Porteous, M.E.; Pujana, M.A.; Radice, P.; Ramser, J.; Rantala, J.; Rashid, M.U.; Rhiem, K.; Rizzolo, P.; Robson, M.E.; Rookus, M.A.; Rossing, C.M.; Ruddy, K.J.; Santos, C.; Saule, C.; Scarpitta, R.; Schmutzler, R.K.; Schuster, H.; Senter, L.; Seynaeve, C.M.; Shah, P.D.; Sharma, P.; Shin, V.Y.; Silvestri, V.; Simard, J.; Singer, C.F.; Skytte, A.-B.; Snape, K.; Solano, A.R.; Soucy, P.; Southey, M.C.; Spurdle, A.B.; Steele, L.; Steinemann, D.; Stoppa-Lyonnet, D.; Stradella, A.; Sunde, L.; Sutter, C.; Tan, Y.Y.; Teixeira, M.R.; Teo, S.H.; Thomassen, M.; Tibiletti, M.G.; Tischkowitz, M.; Tognazzo, S.; Toland, A.E.; Tommasi, S.; Torres, D.; Toss, A.; Trainer, A.H.; Tung, N.; Van Asperen, C.J.; Van Der Baan, F.H.; Van Der Kolk, L.E.; Van Der Luijt, R.B.; Van Hest, L.P.; Varesco, L.; Varon-Mateeva, R.; Viel, A.; Vierstrate, J.; Villa, R.; Von Wachenfeldt, A.; Wagner, P.; Wang-Gohrke, S.; Wappenschmidt, B.; Weitzel, J.N.; Wieme, G.; Yadav, S.; Yannoukakos, D.; Yoon, S.-Y.; Zanzottera, C.; Zorn, K.K.; D’Amico, A.V.; Freedman, M.L.; Pomerantz, M.M.; Chenevix-Trench, G.; Antoniou, A.C.; Neuhausen, S.L.; Ottini, L.; Nielsen, H.R.; Rebbeck, T.R. (2020)
    Pathogenic sequence variants (PSV) in BRCA1 or BRCA2 (BRCA1/2) are associated with increased risk and severity of prostate cancer. Weevaluated whether PSVs inBRCA1/2 were associated with risk of overall prostate cancer or high grade (Gleason 8+) prostate cancer using an international sample of 65 BRCA1 and 171 BRCA2 male PSV carriers with prostate cancer, and 3,388 BRCA1 and 2,880 BRCA2 male PSV carriers without prostate cancer. PSVs in the 30 region of BRCA2 (c.7914+) were significantly associated with elevated risk of prostate cancer compared with reference bin c.1001c.7913 [HR = 1.78; 95% confidence interval (CI), 1.25-2.52; P = 0.001], as well as elevated risk of Gleason 8+ prostate cancer (HR = 3.11; 95% CI, 1.63-5.95; P = 0.001). c.756-c.1000 was also associated with elevated prostate cancer risk (HR = 2.83; 95% CI, 1.71-4.68; P = 0.00004) and elevated risk of Gleason 8+prostate cancer (HR = 4.95; 95% CI, 2.12-11.54; P = 0.0002). No genotype-phenotype associations were detected for PSVs in BRCA1. These results demonstrate that specific BRCA2 PSVs may be associated with elevated risk of developing aggressive prostate cancer. Significance: Aggressive prostate cancer risk in BRCA2 mutation carriers may vary according to the specific BRCA2 mutation inherited by the at-risk individual.
  • Rebbeck, Timothy R.; Mitra, Nandita; Wan, Fei; Sinilnikova, Olga M.; Healey, Sue; McGuffog, Lesley; Mazoyer, Sylvie; Chenevix-Trench, Georgia; Easton, Douglas F.; Antoniou, Antonis C.; Nathanson, Katherine L.; CIMBA Consortium; Nevanlinna, Heli; Aittomäki, Kristiina (2015)
    IMPORTANCE Limited information about the relationship between specific mutations in BRCA1 or BRCA2 (BRCA1/2) and cancer risk exists. OBJECTIVE To identify mutation-specific cancer risks for carriers of BRCA1/2. DESIGN, SETTING, AND PARTICIPANTS Observational study of women who were ascertained between 1937 and 2011 (median, 1999) and found to carry disease-associated BRCA1 or BRCA2 mutations. The international sample comprised 19 581 carriers of BRCA1 mutations and 11 900 carriers of BRCA2 mutations from 55 centers in 33 countries on 6 continents. We estimated hazard ratios for breast and ovarian cancer based on mutation type, function, and nucleotide position. We also estimated RHR, the ratio of breast vs ovarian cancer hazard ratios. A value of RHR greater than 1 indicated elevated breast cancer risk; a value of RHR less than 1 indicated elevated ovarian cancer risk. EXPOSURES Mutations of BRCA1 or BRCA2. MAIN OUTCOMES AND MEASURES Breast and ovarian cancer risks. RESULTS Among BRCA1 mutation carriers, 9052 women (46%) were diagnosed with breast cancer, 2317(12%) with ovarian cancer, 1041 (5%) with breast and ovarian cancer, and 7171 (37%) without cancer. Among BRCA2 mutation carriers, 6180 women (52%) were diagnosed with breast cancer, 682(6%) with ovarian cancer, 272(2%) with breast and ovarian cancer, and 4766 (40%) without cancer. In BRCA1, we identified 3 breast cancer cluster regions (BCCRs) located at c.179 to c.505 (BCCR1; RHR = 1.46; 95% Cl, 1.22-1.74; P = 2 x 10(-6)), c.4328 to c.4945 (BCCR2; RH R = 1.34; 95% Cl, 1.01-1.78; P =.04), and c. 5261 to c.5563 (BCCR2', RHR = 1.38; 95% Cl, 1.22-1.55; P = 6 x 10(-9)). We also identified an ovarian cancer cluster region (OCCR) from c.1380 to c.4062 (approximately exon 11) with RHR = 0.62 (95% Cl, 0.56-0.70; P = 9 x 10(-17)). In BRCA2, we observed multiple BCCRs spanning c.1 to c.596 (BCCR1; RHR = 1.71; 95% Cl, 1.06-2.78; P =.03), c.772 to c.1806 (BCCRI; RHR = 1.63; 95% Cl, 1.10-2.40; P =.01), and c.7394 to c.8904 (BCCR2; RHR = 2.31; 95% Cl, 1.69-3.16; P =.00002). We also identified 3 OCCRs: the first (OCCR1) spanned c.3249 to c.5681 that was adjacent to c.5946delT (6174delT; RHR = 0.51; 95% Cl, 0.44-0.60; P = 6 x 10(-17)). The second OCCR spanned c.6645 to c.7471 (OCCR2; RHR = 0.57; 95% Cl, 0.41-0.80; P =.001). Mutations conferring nonsense-mediated decay were associated with differential breast or ovarian cancer risks and an earlier age of breast cancer diagnosis for both BRCA1 and BRCA2 mutation carriers. CONCLUSIONS AND RELEVANCE Breast and ovarian cancer risks varied by type and location of BRCA1/2 mutations. With appropriate validation, these data may have implications for risk assessment and cancer prevention decision making for carriers of BRCA1 and BRCA2 mutations.
  • Hirvonen, Elina A. M.; Peuhkuri, Saara; Norberg, Anna; Degerman, Sofie; Hannula-Jouppi, Katariina; Välimaa, Hannamari; Kilpivaara, Outi; Wartiovaara-Kautto, Ulla (2019)
  • Selmer, Ilka; Karnetzke, Julia; Kleemann, Christian; Lehtonen, Mari; Mikkonen, Kirsi S.; Kulozik, Ulrich; Smirnova, Irina (2019)
  • Zheng, Guoqiao; Yu, Hongyao; Hemminki, Akseli; Forsti, Asta; Sundquist, Kristina; Hemminki, Kari (2017)
    Male breast cancer is associated with female breast cancer in families but whether male breast cancer clusters with other discordant cancers has not been studied. As concordant male breast cancers are utterly rare, discordant associations of male breast cancer with other cancers may reveal genetic and possible environmental risk factors contributing to male breast cancer susceptibility. We calculated relative risks (RRs) for male breast cancer in families with discordant cancers, and conversely, for discordant cancers in families of male breast cancer patients, based on 15.7 million individuals in the Swedish Family-Cancer Database. Among 1428 male breast cancer patients, 16.2% had a female relative diagnosed with breast cancer. Ovarian and female anal cancers showed the strongest associations with male breast cancer (p value <0.0005). The other significant associations included colorectal, small intestinal, and thyroid cancers, cancer of unknown primary and non-Hodgkin lymphoma but these were each based on a single positive association with male breast cancer. The RRs for male breast cancer were increased in families in which multiple patients were diagnosed with diverse cancers, reaching an RR of 2.58 when three or more family members were affected. The results suggest that male breast cancer shares susceptibility with a number of other cancers but confirmation is needed in other datasets.
  • Zheng, Guoqiao; Yu, Hongyao; Kanerva, Anna; Försti, Asta; Sundquist, Kristina; Hemminki, Kari (2018)
    Ovarian cancer is a heterogeneous disease. Data regarding familial risks for specific proband, age at diagnosis and histology are limited. Such data can assist genetic counseling and help elucidate etiologic differences among various histologic types of ovarian malignancies. By using the Swedish Family-Cancer Database, we calculated relative risks (RRs) for detailed family histories using a two-way comparison, which implied e.g. estimation of RRs for overall ovarian cancer when family history was histology-specific ovarian cancer, and conversely, RRs for histology-specific ovarian cancer when family history was overall ovarian cancer. In families of only mother, only sisters or both mother and sisters diagnosed with ovarian cancer, cancer risks for ovary were 2.40, 2.59 and 10.40, respectively; and were higher for cases diagnosed before the age of 50 years. All histological types showed a familial risk in two-way analyses, except mucinous and sex cord-stromal tumors. RRs for concordant histology were found for serous (2.47), endometrioid (3.59) and mucinous ovarian cancers (6.91). Concordant familial risks were highest for mucinous cancer; for others, some discordant associations, such as endometrioid-undifferentiated (9.27) and serous-undifferentiated (4.80), showed the highest RRs. Familial risks are high for early-onset patients and for those with multiple affected relatives. Sharing of different histological types of ovarian cancer is likely an indication of the complexity of the underlying mechanisms.
  • Muranen, Taru A.; Greco, Dario; Blomqvist, Carl; Aittomäki, Kristiina; Khan, Sofia; Hogervorst, Frans; Verhoef, Senno; Pharoah, Paul D. P.; Dunning, Alison M.; Shah, Mitul; Luben, Robert; Bojesen, Stig E.; Nordestgaard, Borge G.; Schoemaker, Minouk; Swerdlow, Anthony; Garcia-Closas, Montserrat; Figueroa, Jonine; Doerk, Thilo; Bogdanova, Natalia V.; Hall, Per; Li, Jingmei; Khusnutdinova, Elza; Bermisheva, Marina; Kristensen, Vessela; Borresen-Dale, Anne-Lise; Peto, Julian; Silva, Isabel dos Santos; Couch, Fergus J.; Olson, Janet E.; Hillemans, Peter; Park-Simon, Tjoung-Won; Brauch, Hiltrud; Hamann, Ute; Burwinkel, Barbara; Marme, Frederik; Meindl, Alfons; Schmutzler, Rita K.; Cox, Angela; Cross, Simon S.; Sawyer, Elinor J.; Tomlinson, Ian; Lambrechts, Diether; Moisse, Matthieu; Lindblom, Annika; Margolin, Sara; Hollestelle, Antoinette; Martens, John W. M.; Fasching, Peter A.; Beckmann, Matthias W.; Nevanlinna, Heli; NBCS Investigators; KConFab AOCS Investigators; Breast Canc Assoc Consortium (2017)
    Purpose: CHEK2*1100delC is a founder variant in European populations that confers a two-to threefold increased risk of breast cancer (BC). Epidemiologic and family studies have suggested that the risk associated with CHEK2*1100delC is modified by other genetic factors in a multiplicative fashion. We have investigated this empirically using data from the Breast Cancer Association Consortium (BCAC). Methods: Using genotype data from 39,139 (624 1100delC carriers) BC patients and 40,063 (224) healthy controls from 32 BCAC studies, we analyzed the combined risk effects of CHEK2*1100delC and 77 common variants in terms of a polygenic risk score (PRS) and pairwise interaction. Results: The PRS conferred odds ratios (OR) of 1.59 (95% CI: 1.212.09) per standard deviation for BC for CHEK2*1100delC carriers and 1.58 (1.55-1.62) for noncarriers. No evidence of deviation from the multiplicative model was found. The OR for the highest quintile of the PRS was 2.03 (0.86-4.78) for CHEK2*1100delC carriers, placing them in the high risk category according to UK NICE guidelines. The OR for the lowest quintile was 0.52 (0.16-1.74), indicating a lifetime risk close to the population average. Conclusion: Our results confirm the multiplicative nature of risk effects conferred by CHEK2*1100delC and the common susceptibility variants. Furthermore, the PRS could identify carriers at a high lifetime risk for clinical actions.
  • Pelttari, Liisa M.; Kiiski, Johanna I.; Ranta, Salla; Vilske, Sara; Blomqvist, Carl; Aittomaki, Kristiina; Nevanlinna, Heli (2015)
    Majority of the known breast cancer susceptibility genes have a role in DNA repair and the most important high-risk genes BRCA1 and BRCA2 are specifically involved in the homologous recombination repair (HRR) of DNA double-strand breaks. A central player in HRR is RAD51 that binds DNA at the damage site. The RAD51 paralogs RAD51B, RAD51C, RAD51D, XRCC2, and XRCC3 facilitate the binding of RAD51 to DNA. While germline mutations in RAD51C and RAD51D are associated with high ovarian cancer risk and RAD51B polymorphisms with breast cancer, the contribution of RAD51, XRCC3, and XRCC2 is more unclear. To investigate the role of RAD51, XRCC3, and XRCC2 in breast cancer predisposition and to identify putative recurrent founder mutations in the Finnish population where such mutations have been observed in most of the currently known susceptibility genes, we screened 182 familial Finnish breast or ovarian cancer patients for germline variation in the RAD51 and XRCC3 genes and 342 patients for variation in XRCC2, with a subset of the patients selected on the basis of decreased RAD51 protein expression on tumors. We also performed haplotype analyses for 1516 breast cancer cases and 1234 controls to assess the common variation in these genes. No pathogenic mutations were detected in any of the genes and the distribution of haplotypes was similar between cases and controls. Our results suggest that RAD51, XRCC3, and XRCC2 do not substantially contribute to breast cancer predisposition in the Finnish population.
  • GEMO Study Collaborators; EMBRACE Collaborators; GC-HBOC Study Collaborators; ABCTB Investigators; HEBON Investigators; BCFR Investigators; OCGN Investigators; Feng, Helian; Gusev, Alexander; Pasaniuc, Bogdan; Aittomäki, Kristiina; Blomqvist, Carl; Dunning, Alison M.; Kiiski, Johanna I.; Muranen, Taru A.; Nevanlinna, Heli; Zheng, Wei (2020)
    Previous transcriptome-wide association studies (TWAS) have identified breast cancer risk genes by integrating data from expression quantitative loci and genome-wide association studies (GWAS), but analyses of breast cancer subtype-specific associations have been limited. In this study, we conducted a TWAS using gene expression data from GTEx and summary statistics from the hitherto largest GWAS meta-analysis conducted for breast cancer overall, and by estrogen receptor subtypes (ER+ and ER-). We further compared associations with ER+ and ER- subtypes, using a case-only TWAS approach. We also conducted multigene conditional analyses in regions with multiple TWAS associations. Two genes, STXBP4 and HIST2H2BA, were specifically associated with ER+ but not with ER- breast cancer. We further identified 30 TWAS-significant genes associated with overall breast cancer risk, including four that were not identified in previous studies. Conditional analyses identified single independent breast-cancer gene in three of six regions harboring multiple TWAS-significant genes. Our study provides new information on breast cancer genetics and biology, particularly about genomic differences between ER+ and ER- breast cancer.
  • Webb, P. M.; Na, R.; Weiderpass, E.; Adami, H. O.; Anderson, K. E.; Bertrand, K. A.; Botteri, E.; Brasky, T. M.; Brinton, L. A.; Chen, C.; Doherty, J. A.; Lu, L.; McCann, S. E.; Moysich, K. B.; Olson, S.; Petruzella, S.; Palmer, J. R.; Prizment, A. E.; Schairer, C.; Setiawan, V. W.; Spurdle, A. B.; Trabert, B.; Wentzensen, N.; Wilkens, L.; Yang, H. P.; Yu, H.; Risch, H. A.; Jordan, S. J. (2019)
    Background: Regular use of aspirin has been associated with a reduced risk of cancer at several sites but the data for endometrial cancer are conflicting. Evidence regarding use of other analgesics is limited. Patients and methods: We pooled individual-level data from seven cohort and five case-control studies participating in the Epidemiology of Endometrial Cancer Consortium including 7120 women with endometrial cancer and 16 069 controls. For overall analyses, study-specific odds ratios (ORs) and 95% confidence intervals (CI) were estimated using logistic regression and combined using random-effects meta-analysis; for stratified analyses, we used mixed-effects logistic regression with study as a random effect. Results: At least weekly use of aspirin and non-aspirin nonsteroidal anti-inflammatory drugs (NSAIDs) was associated with an approximately 15% reduced risk of endometrial cancer among both overweight and obese women (OR 1/4 0.86 [95% CI 0.760.98] and 0.86 [95% CI 0.76-0.97], respectively, for aspirin; 0.87 [95% CI 0.76-1.00] and 0.84 [0.74-0.96], respectively, for nonaspirin NSAIDs). There was no association among women of normal weight (body mass index<25 kg/ m2, Pheterogeneity 0.04 for aspirin, Pheterogeneity 1/4 0.003 for NSAIDs). Among overweight and obese women, the inverse association with aspirin was stronger for use 2-6 times/ week (OR 1/4 0.81, 95% CI 0.68-0.96) than for daily use (0.91, 0.80-1.03), possibly because a high proportion of daily users use low-dose formulations. There was no clear association with use of acetaminophen. Conclusion: Our pooled analysis provides further evidence that use of standard-dose aspirin or other NSAIDs may reduce risk of endometrial cancer among overweight and obese women.
  • Khan, Daulat Haleem; Bashir, Sajid; Correia, Alexandra; Khan, Muhammad Imran; Figueiredo, Patricia; Santos, Hélder A.; Peltonen, Leena (2019)
    The aim of the present study was to prepare niosome formulations for the simultaneous encapsulation, dual drug therapy, of two anticancer drugs by the ecological probe sonication method. Poloxamer and sorbitan monostearate were used as surface active agents in niosomes, and the water soluble doxorubicin and poorly-water soluble paclitaxel were used as anticancer drugs. Thorough physicochemical analysis were performed for the niosomes, and their cytotoxicity and activity were evaluated on MCF-7 and PC3-MM2 cancer cell lines. Prepared niosomes were small in size with sizes ranging from 137 nm to 893 nm, and entrapment efficiencies were high, ranging from 91.24% to 99.99%. During the four weeks stability testing, the particle size remained stable. The niosomal formulations showed in vitro sustained drug release profiles for doxorubicin and clearly increased the dissolution rate of poorly water soluble paclitaxel. The incorporation of both the drugs into niosomes improved cell penetration and antiproliferative activity of the drugs PC3-MM2 cell lines. As a conclusion, doxorubicin and paclitaxel loaded niosome formulations resulted in relatively stable, small sized niosomes with improved drug release profiles, low toxicity, better cell penetration and antiproliferative activity. The niosomes showed synergistic effect due to the presence of both drugs, which can overcome multidrug resistance.